Cloning, expression and electrophysiological characterization of glycine receptor alpha subunit from zebrafish

The glycine receptor is a ligand-gated anion channel protein, providing inhibitory drive within the nervous system. We report here the isolation and functional characterization of a novel α subunit (αZ1) of the glycine receptor from adult zebrafish (Danio rerio) brain. The predicted amino acid sequence is 86%, 81% and 77% identical to mammalian isoforms α1, α3 and α2, respectively. αZ1 exhibits many of the molecular features of mammalian α1, but the sequence patterns in the M4 and C-terminal domains are more similar to α2/α3. Phylogenetic analysis indicates that αZ1 is more closely related to the mammalian α1 subunits, being positioned, however, on a distinct branch. The αZ1 messenger RNA is 9.5 kb, similar to that described previously for α1 messenger RNAs. When expressed in Xenopus oocytes or a human cell line (BOSC 23), αZ1 forms a homomeric receptor which is activated by glycine and antagonized by strychnine. This receptor demonstrates unexpectedly high sensitivity to taurine and can also be activated by GABA. These results are consistent with physiological findings in lamprey and goldfish, and they suggest that this teleost fish glycine receptor displays a lower selectivity to neurotransmitters than that reported for glycine mammalian receptors.